crossing96/oncoscreening huggingface dataset:
Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation.	BACKGROUND: Metastasis is a major obstacle in the treatment of bladder cancer (BC). Circular RNAs exert various functions in the aggressive biological behaviour of cancers. In this study, we aimed to elucidate how circPICALM influences BC metastasis. METHODS: The expression of circPICALM was analysed by real-time PCR. The tumourigenic properties of BC cells were evaluated using in vitro migration, invasion, and wound healing assays and an in vivo footpad model. The interaction between circPICALM and miR-1265 was confirmed by pull-down and dual-luciferase reporter assays and biotin-labelled miRNA capture. The interaction of STEAP4 and focal adhesion kinase (FAK) was confirmed by co-immunoprecipitation. FINDINGS: CircPICALM was downregulated in BC tissues, and low circPICALM expression was related to advanced T stage, high grade, lymph node positivity and poor overall survival. Overexpression of circPICALM inhibited the metastasis of BC cells, and DHX9 negatively regulated circPICALM levels. CircPICALM colocalized with miR-1265 and acted as a sponge for this miRNA, and the pro-invasion effect of miR-1265 was abolished by circPICALM overexpression. STEAP4, a target of miR-1265, suppressed metastasis; it bound to FAK to prevent autophosphorylation at Y397 and influenced EMT in BC cells. INTERPRETATION: CircPICALM can inhibit BC metastasis and bind to miR-1265 to block its pro-invasion activity. STEAP4 is a target of miR-1265 and is related to FAK phosphorylation and EMT. FUND: This research was supported by National Natural Science Foundation of China, No.81772728, National Natural Science Foundation of China, No.81772719, National Natural Science Foundation of China No.81572514.	bladder
Socioeconomic Status-Related Parameters as Predictors of Competing (Non-Bladder Cancer) Mortality after Radical Cystectomy.	OBJECTIVE: To investigate the impact of socioeconomic status-related parameters on competing (non-bladder cancer) mortality after radical cystectomy. PATIENTS AND METHODS: A total of 1,268 consecutive patients who underwent radical cystectomy for urothelial or undifferentiated bladder cancer at our institution between 1993 and 2016 with a mean age of 69 years (median 70 years) were studied. The mean -follow-up of the censored patients was 7.2 years (median 5.7 years). Proportional hazard models for competing risk were used to identify predictors of non-bladder cancer (competing) mortality. The following parameters were included into multivariate analyses: age, American Society of Anesthesiologists physical status classification, Charlson score, gender, level of education, smoking status, marital status, local tumour stage, lymph node status, adjuvant and neoadjuvant chemotherapy. RESULTS: Besides age and both comorbidity classifications, the socioeconomic status-related parameters gender (female versus male, hazard ratio [HR] 0.58, 95% CI 0.40-0.84, p = 0.0042), level of education (university degree or master craftsman versus others, HR 0.76, 95% CI 0.56-0.1.03, p = 0.0801), smoking status (current smoking versus others, HR 1.47, 95% CI 1.10-1.96, p = 0.0085) and marital status (married versus others, HR 0.68, 95% CI 0.50-0.92, p = 0.0133) were independent predictors of competing mortality after radical cystectomy. If considered in combination (multiplication of HRs), the prognostic impact of socioeconomic parameters superseded that of the investigated comorbidity classifications. CONCLUSION: Socioeconomic status-related parameters may provide important information on the long-term competing mortality risk after radical cystectomy supplementary to chronological age and comorbidity.	bladder
Delivery of TRAIL-expressing plasmid DNA to cancer cells in vitro and in vivo using aminoglycoside-derived polymers.	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that can preferentially induce apoptosis in cancer cells over normal cells. The transmembrane form of TRAIL has been shown to elicit much stronger activity than its soluble counterpart but delivery is a potential challenge. Here, we investigated the potential of aminoglycoside-derived polymers to enhance delivery of a plasmid (pEF-TRAIL) that expresses the transmembrane form of TRAIL in order to determine the effect on cell death in vitro and tumor growth in vivo. Transgene delivery efficacy and toxicity of aminoglycoside-derived polymers was first evaluated using a GFP-expressing plasmid (pEF-GFP) at different plasmid amounts and plasmid : polymer ratios in UMUC3 bladder cancer and HeLa cervical cancer cells. Delivery of the TRAIL plasmid using aminoglycoside-derived polymers resulted in up to 60% cell death in UMUC3 and HeLa cells; TRAIL protein expression was confirmed using Western blots. TRAIL plasmid delivery resulted in a decrease in cellular procaspase-8 and an increase in TRAIL receptor DR5 levels, suggesting a role for the death receptor and caspase cascade in TRAIL-mediated apoptosis. The TRAIL plasmid did not cause cell death in normal human or mouse fibroblasts. The in vivo delivery of the TRAIL plasmid using a paromomycin-derived polymer resulted in significant reduction in tumor burden and increased survival in tumor-bearing live mice.	bladder
The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study.	After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.	bladder
The Safety and Short-term Outcomes of Leukocyte Depleted Autologous Transfusions During Radical Cystectomy.	OBJECTIVE: To examine long- and short-term outcomes using cell salvage with a commercially available leukocyte depletion filter following radical cystectomy in an oncologic population. MATERIALS AND METHODS: One hundred and fifty-seven patients, 87 of whom received a cell salvage transfusion, were retrospectively identified from chart review. Ninety-day outcomes as well as long-term mortality and cancer recurrence data were collected. Chi-square, Student's t, or Mann-Whitney U tests were used as appropriate. Multivariable regressions of survival were performed with a Cox proportional-hazards model. RESULTS: Those who received a cell salvage transfusion did not show any differences in rate of cancer recurrence (23%) vs those who did not receive a cell salvage transfusion (24%; P = .85). There were also no differences noted in mortality rates between the 2 populations (12% vs 17%; P = .36). Furthermore, no differences were noted in postoperative complication rates, length of hospital stay, 90-day culture positive infections or readmissions (P >.05). CONCLUSION: There are no significant differences in short-term or long-term patient outcomes between those who did and did not receive an intraoperative cell salvage transfusion. Cell salvage transfusions with a leukocyte depletion filter are safe and effective methods to reduce the need for allogeneic blood transfusions while controlling for the theoretical risk of metastatic spread.	bladder
The impact of underinsurance on bladder cancer diagnosis, survival, and care delivery for individuals under the age of 65 years.	BACKGROUND: Health insurance is a key mediator of health care disparities. Outcomes in bladder cancer, one of the costliest diseases to treat, may be especially sensitive to a patient's insurance status. METHODS: The Surveillance, Epidemiology, and End Results registry and the National Cancer Data Base were used to identify individuals younger than 65 years who were diagnosed with bladder cancer from 2007 to 2014. The associations between the insurance status (privately insured, insured by Medicaid, or uninsured) and the following outcomes were evaluated: diagnosis with advanced disease, cancer-specific survival, delay in treatment longer than 90 days, treatment in a high-volume hospital, and receipt of neoadjuvant chemotherapy (NAC). RESULTS: Compared with those with private insurance, uninsured and Medicaid-insured individuals were nearly twice as likely to receive a diagnosis of muscle-invasive bladder cancer (odds ratio [OR] for uninsured individuals, 1.90; 95% confidence interval [CI], 1.70-2.12; OR for Medicaid-insured individuals, 2.03; 95% CI, 1.87-2.20). They were also more likely to die of bladder cancer (adjusted hazard ratio [AHR] for uninsured individuals, 1.49; 95% CI, 1.31-1.71; AHR for Medicaid-insured individuals, 1.61; 95% CI, 1.46-1.79). Delays in treatment longer than 90 days were more likely for uninsured (OR, 1.36; 95% CI, 1.12-1.65) and Medicaid-insured individuals (OR, 1.22; 95% CI, 1.03-1.44) in comparison with the privately insured. Uninsured patients had lower odds of treatment at a high-volume facility, and Medicaid-insured patients had lower odds of receiving NAC (P < .001 for both). CONCLUSIONS: Compared with privately insured individuals, uninsured and Medicaid-insured individuals experience worse prognoses and poorer care quality. Expanding high-quality insurance coverage to marginalized populations may help to reduce the burden of this disease.	bladder
Prognostic utility of the combination of pretreatment monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with NMIBC after transurethral resection.	Aim: To investigate and validate predictive value of combination of pretreatment monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) for disease free survival (DFS) and overall survival (OS) in nonmuscle invasive bladder cancer after transurethral resection. Materials & methods: Total 358 patients enrolled were assigned into three (MLR-NLR 0, 1 and 2) groups per the cut-off values of MLR and NLR. Results: Kaplan-Meier curves showed MLR, NLR and their combination were statistically associated with DFS (p < 0.001) and OS (p < 0.001). Univariate and multivariate COX regression analyses revealed that combination of MLR with NLR was an independent prognostic predictor for both DFS (HR: 3.080; 95% CI: 1.870-5.074; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0) and OS (HR: 2.815; 95% CI: 1.778-4.456; p < 0.001 for MLR-NLR 2 vs MLR-NLR 0). Calibration plots and decision curve analysis exhibited combination of MLR and NLR had good calibration accuracy with potential clinical usefulness. Conclusion: Combined MLR and NLR is a prognostic predictive biomarker in nonmuscle invasive bladder cancer after transurethral resection.	bladder
AMPK-mTOR-ULK1 axis activation-dependent autophagy promotes hydroxycamptothecin-induced apoptosis in human bladder cancer cells.	10-hydroxycamptothecin (HCPT), a natural plant extract, exerts anticancer capacity. HCPT has been reported to induce apoptosis and autophagy in human cancer cells. The interaction between autophagy and apoptosis induced by HCPT and the molecular mechanism in bladder cancer cells were investigated in this study. Our results confirmed that HCPT suppressed cell viability and migration and caused cell-cycle arrest in T24 and 5637. Then, we used Z-VAD(OMe)-FMK to clarify that apoptosis induced by HCPT was mediated by caspase. Moreover, HCPT boosted autophagy through activating the AMPK/mTOR/ULK1 pathway. Blocking autophagy by 3-methyladenine, the adenosine monophosphate-activated protein kinase (AMPK) inhibitor dorsomorphin and siATG7 reversed HCPT-induced cytotoxicity. Conversely, rapamycin and the AMPK activator AICAR enhanced growth inhibition and cell apoptosis, suggesting that autophagy played a proapoptosis role. Taken together, our findings showed that HCPT-induced autophagy mediated by the AMPK pathway in T24 and 5637 cell lines, which reinforced the apoptosis, indicating that HCPT together with autophagy activator would be a novel strategy for clinical treatment in bladder cancer.	bladder
Spontaneous renoalimentary fistula as a complication of upper tract urothelial carcinoma: unknown complication of a rare disease.	Fistulae of the upper urinary tract with the alimentary tract are rare. Most cases of renoalimentary fistulae are secondary to penetrating trauma, which may be iatrogenic or due to locally invasive benign infective processes or complicated nephrolithiasis, or following surgical procedures. Spontaneous renoalimentary fistulae developing secondary to locally advanced malignancies, namely renal cell carcinoma, are very rare, and unknown due to upper tract transitional cell carcinoma. We present a case where a 60-year-old man, presented with clinical symptoms suggestive of upper gastrointestinal tract pathology, with no urological complaints and was diagnosed to have a renoalimentary fistula on cross-sectional imaging and upper gastrointestinal endoscopy with histopathology of duodenal growth biopsy showing high-grade transitional cell carcinoma. Due to unresectable nature of this mass, this patient had a gastric and biliary diversion and was started on palliative chemotherapy. Renoalimentary fistulae due to benign inflammatory causes may be treated by nephrectomy with or without resection of the involved bowel segment. However, all malignant fistulae have to be treated as locally advanced tumours and en bloc resection should be attempted whenever feasible.	bladder
Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis.	BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution. METHODS: LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 and n = 94). RESULTS: NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched for FGFR3 mutations and depleted for TP53 and RB1 mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts. CONCLUSIONS: Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.	bladder
A Population-based Study of Ureteroenteric Strictures After Open and Robot-assisted Radical Cystectomy.	OBJECTIVE: To evaluate differences in the incidence of benign ureteroenteric stricture, we compared stricture rates of robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC) using Surveillance, Epidemiology, and End Results-Medicare data. METHODS: We identified 332 RARC and 1449 ORC performed between 2009 and 2014 to determine stricture rates at 6, 12, and 24 months following surgery. We defined ureteroenteric stricture as the need for procedural intervention. Additionally, we compared the incidence of stricture diagnosis. Multivariable proportional hazards regression was performed to determine factors associated with stricture development. RESULTS: The incidence of ureteroenteric stricture at 6 and 12 months was higher for RARC vs ORC at 12.1% vs 7.0% (P < .01) and 15.0% vs 9.5% (P = .01), respectively. RARC vs ORC stricture incidence at 2 years did not differ significantly at 14.6% vs 11.4% (P = .29). Similarly, the stricture diagnosis rates were significantly lower following ORC at 6, 12, and 24 months (P < .05). In adjusted analysis, RARC (HR 1.64, 95%CI 1.23-2.19) and preoperative hydronephrosis (HR 1.51, 95% CI 1.17-1.94) were associated with the development of stricture. Higher hospital volume was associated with a lower risk of stricture (HR 0.40, 95%CI 0.26-0.63). CONCLUSION: RARC is associated with a higher rate of ureteroenteric stricture diagnosis and intervention on a population-based level that is mitigated by higher hospital volume. A significant study limitation is inability to differentiate extracorporeal vs intracorporeal diversion. However, a stricture complication compounds the financial burden of care and efforts must be pursued to improve this surgical outcome.	bladder
Bladder tissue characterization using probe-based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction.	Existing approaches for early-stage bladder tumor diagnosis largely depend on invasive and time-consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real-time tumor diagnosis can enable immediate laser-based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real-time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe-based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low- and high-grade tumor.	bladder
Comparison of gemcitabine and anthracycline antibiotics in prevention of superficial bladder cancer recurrence.	BACKGROUND: Because of the failure, shortage and related toxicities of Bacillus Calmette-Guérin (BCG), the other intravesical chemotherapy drugs are also widely used in clinical application. Gemcitabine and anthracycline antibiotics (epirubicin and pirarubicin) are widely used as first-line or salvage therapy, but which drug is better is less discussed. METHODS: A total of 124 primary NMIBC patients administered intravesical therapy after transurethral resection of bladder tumor (TURBT) at Nanjing Drum Tower hospital from January 1996 to July 2018. After TURBT, all patients accepted standard intravesical chemotherapy. Recurrence was defined as the occurrence of a new tumor in the bladder. Progression was defined as confirmed tumor invading muscular layer. Treatment failure was defined as need for radical cystectomy (RC), systemic chemotherapy and radiation therapy. RESULTS: Of the 124 patients who underwent intravesical chemotherapy, 84 patients were given gemcitabine, 40 patients were given epirubicin or pirarubicin, with mean follow-up times (mean ± SD) of (34.8 ± 17.9) and (35.9 ± 22.1) months respectively. The clinical and pathological features of patients show no difference between two groups. Recurrence rate of patients given gemcitabine was 8.33% (7 out of 84), the recurrence rate was 45% (18 out of 40) for epirubicin or pirarubicin (P < 0.0001). The progression rates of gemcitabine, anthracycline antibiotics groups were 2.38% (2 out of 84) and 20% (8 out of 40), respectively (P < 0.001). The rate of treatment failure is 8.33% (7 out of 84) and 25% (10 out of 40), respectively (P = 0.012). Gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence (HR = 0.165, 95% CI 0.069-0.397, P = 0.000), progression (HR = 0.160, 95% CI 0.032-0.799, P = 0.026) and treatment failure (HR = 0.260, 95% CI 0.078-0.867, P = 0.028). CONCLUSION: In conclusion, gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence, progression and treatment failure. Gemcitabine could be considered as a choice for these patients who are not suitable for BCG.	bladder
A population-based cohort study examining the association of documented bladder diverticulum and bladder cancer risk in urology patients.	OBJECTIVES: Studies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer. METHODS: We identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan's National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model. RESULTS: There was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74-3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities. CONCLUSION: In this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required.	bladder